Is OTUD5 p.Pro504Leu (c.1511C>T) pathogenic?

OTUD5 p.Pro504Leu (c.1511C>T) is classified Uncertain significance in OTUD5 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-20). AlphaMissense: likely benign (0.2862); Absent from gnomAD v4.1; Associated with multiple congenital anomalies-neurodevelopmental syndrome, X-linked.

What condition is associated with OTUD5 p.Pro504Leu (c.1511C>T)?

OTUD5 p.Pro504Leu (c.1511C>T) is associated with multiple congenital anomalies-neurodevelopmental syndrome, X-linked (ClinVar).

How common is OTUD5 p.Pro504Leu (c.1511C>T) in the general population?

OTUD5 p.Pro504Leu (c.1511C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTUD5 p.Pro504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.2862) — an in-silico prediction, not a clinical call.

OTUD5 p.Pro504Leu

c.1511C>T · rs2519709235 · VCV1710154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple congenital anomalies-neurodevelopmental syndrome, X-linked

Computational evidence

Protein change
AlphaMissense	0.2862	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 2,696 bp · p 4.2e-11 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P509L vs ClinVar P504L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OTUD5
Protein: p.Pro504Leu
Coding: c.1511C>T
MANE Select: NM_001136157
dbSNP: rs2519709235
Type: single nucleotide variant
Location: chrX:48923701 (GRCh38)
Structure: AlphaFold pLDDT 66.15 · 3 PDB

Full OTUD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple congenital anomalies-neurodevelopmental syndrome, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OTUD5 p.Arg515Trp Likely pathogenic ★★ ⚠ same condition
OTUD5 p.Ser539Leu Uncertain significance ★★ ⚠ same condition
OTUD5 p.Gly489Ser Pathogenic ★ ⚠ same condition
OTUD5 p.Met288Thr Likely pathogenic ★ same condition
OTUD5 p.Ala223Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
OTUD5 p.Arg274Trp Uncertain significance ★ ⚠ same condition
OTUD5 p.Asp51Asn Uncertain significance ★ ⚠ same condition
OTUD5 p.Gln374Arg Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/otud5-p-pro504leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown